The overall objective of the proposed research is to gain further knowledge of the mechanisms that regulate growth, differentiation, and survival of insulin-containing pancreatic islet B cells. These aspects of islet B cell function will be studied in islets enzymatically isolated from the pancreases of newborn rats and maintained in monolayer culture in vitro. Preliminary findings indicate that three groups of substances: (1) purified "growth factors", (2) cyclic nucleotides, and (3) undefined factors in serum-free conditioned medium from cultured fibroblastic cells can promote survival, replication, and improved secretory function of insulin-containing B cells in monolayer culture. These interactions will be studied further. Also, attempts will be made to purify and characterize the fibroblast-derived factor(s) with trophic effects on pancreatic islet B cells. Human skin fibroblasts from normal and diabetic adult subjects will also be examined for potential effects on cultured rat islet B cells.